Professional Education

  • Doctor of Medicine, Heinrich-Heine-University (2017)

All Publications

  • Controlled isoflurane anesthesia exposure is required for reliable behavioral testing in murine surgical models. Journal of pharmacological sciences Toyama, K., Spin, J. M., Abe, Y., Suzuki, Y., Deng, A. C., Wagenhauser, M. U., Yoshino, T., Mulorz, J., Liu, S., Tsao, P. S., Mogi, M. 2019


    We investigated the effects of variations in anesthesia exposure time prior to conducting anxiety response behavioral testing in sham controls from an experimental murine model. The staying time in the center area of the Open Field test in the "long exposure" group was significantly decreased compared to that of the "short exposure" group. Significant correlation was found between anesthesia time and the duration of staying time in the center area. We conclude that anesthesia time may have a significant impact on behavioral anxiety testing in this context, and advise careful control of this parameter in protocol optimization in related surgical animal models.

    View details for DOI 10.1016/j.jphs.2019.03.007

    View details for PubMedID 31133404

  • Clinical outcomes after direct and indirect surgical venous thrombectomy for inferior vena cava thrombosis JOURNAL OF VASCULAR SURGERY-VENOUS AND LYMPHATIC DISORDERS Wagenhaeuser, M. U., Dimopoulos, C., Antakyali, K., Meyer-Janiszewski, Y. K., Mulorz, J., Ibing, W., Ertas, N., Spin, J. M., Schelzig, H., Duran, M. 2019; 7 (3): 333-+
  • Clinical outcomes after direct and indirect surgical venous thrombectomy for inferior vena cava thrombosis. Journal of vascular surgery. Venous and lymphatic disorders Wagenhauser, M. U., Dimopoulos, C., Antakyali, K., Meyer-Janiszewski, Y. K., Mulorz, J., Ibing, W., Ertas, N., Spin, J. M., Schelzig, H., Duran, M. 2019


    OBJECTIVE: Inferior vena cava thrombosis is rare, but patients are at high risk for development of a post-thrombotic syndrome (PTS) in the long term. Surgical approaches include indirect transfemoral venous thrombectomy (iTFVT) and direct open venous thrombectomy (dOVT). This study reports patient outcomes after iTFVT and dOVT for inferior vena cava thrombosis covering a 25-year follow-up period.METHODS: The study period was from January 1, 1982, to December 31, 2013. Data were retrieved from archived medical records, and patients were invited for a detailed phlebologic follow-up examination (DPFE). Health-related quality of life was assessed with the 36-Item Short Form Health Survey questionnaire. Patient survival, patency rates, and freedom from PTS were calculated using Kaplan-Meier estimation with log-rank testing. The chi2 test with Yates continuity correction and logistic regression analysis were applied to identify associations between risk factors or coagulation disorders, mortality, and PTS.RESULTS: Complete medical records were available for 152 patients. Patients' 5-year survival was 91%± 3%, and 5-year primary and secondary patency rates were 80%± 3% and 94%± 2%. Freedom from PTS after 25years was 84%± 6%. No differences for patient survival, patency rates, or freedom from PTS were identified between iTFVT, dOVT, and a combination of both procedures. Antithrombin III deficiency was the most common coagulation disorder, and patients' physical function and social function were impaired compared with those found in German normative data (P< .05). Norisk factor or coagulation disorder was associated with survival or PTS.CONCLUSIONS: Open surgical venous thrombectomy is safe and delivers satisfying short- and long-term outcomes compared with endovascular approaches. It remains valuable for patients who are not eligible for other interventional therapies.

    View details for PubMedID 30853561

  • Chronic Nicotine Exposure Induces Murine Aortic Remodeling and Stiffness Segmentation-Implications for Abdominal Aortic Aneurysm Susceptibility FRONTIERS IN PHYSIOLOGY Wagenhaeuser, M. U., Schellinger, I. N., Yoshino, T., Toyamau, K., Kayamau, Y., Deng, A., Guentheru, S. P., Petzold, A., Mulorz, J., Mulorz, P., Hasenfuss, G., Ibing, W., Elvers, M., Schuster, A., Ramasubramanian, A. K., Adam, M., Schelzig, H., Spin, J. M., Raaz, U., Tsao, P. S. 2018; 9
  • MicroRNA-Mediated Therapy Modulating Blood-Brain Barrier Disruption Improves Vascular Cognitive Impairment. Arteriosclerosis, thrombosis, and vascular biology Toyama, K., Spin, J. M., Deng, A. C., Huang, T., Wei, K., Wagenhauser, M. U., Yoshino, T., Nguyen, H., Mulorz, J., Kundu, S., Raaz, U., Adam, M., Schellinger, I. N., Jagger, A., Tsao, P. S. 2018


    OBJECTIVE: There are currently no effective treatments for the prevention of dementia associated with vascular cognitive impairment. MicroRNAs regulate gene expression at the post-transcriptional level and play key roles in vascular disorders. TNFalpha (tumor necrosis factor-alpha) regulates blood-brain barrier breakdown through modification of cerebral tight junctions. Here, we sought key TNFalpha-responsive microRNAs that might influence blood-brain barrier breakdown via cerebral tight junction disruption in vascular cognitive impairment.APPROACH AND RESULTS: Using a mouse model of vascular cognitive impairment, chronic cerebral hypoperfusion within the white matter was induced with bilateral common carotid artery stenosis (BCAS) surgery. TNFalpha gene expression was increased in white matter post-BCAS surgery, and TNFalpha stimulation decreased claudin-5, ZO-1 (tight-junction protein 1), and occludin gene expression in murine brain endothelial cells. In silico analysis predicted 8 candidate microRNAs as regulators of claudin-5, ZO-1, and occludin gene expression. Of these, only miR-501-3p was upregulated by TNFalpha in vitro and was upregulated in the white matter after BCAS surgery. Further, miR-501-3p directly bound to the 3'-untranslated region of human ZO-1 and downregulated transendothelial electric resistance. In vivo administration of a locked nucleic acid -modified antisense oligonucleotide versus miR-501-3p suppressed BCAS-induced reduction of ZO-1 gene expression and blood-brain barrier disruption within the white matter and significantly ameliorated working memory deficits after BCAS surgery.CONCLUSIONS: We here provide the first evidence that the TNFalpha-miR-501-3p-ZO-1 axis plays an important role in the pathogenesis of cerebral hypoperfusion-induced working memory deficits and white matter lesions, as a result of blood-brain barrier breakdown via tight junction disruption. Therapeutic manipulation of miR-501-3p holds promise for limiting vascular cognitive impairment progression.

    View details for PubMedID 29650692

  • Chronic Nicotine Exposure Induces Murine Aortic Remodeling and Stiffness Segmentation-Implications for Abdominal Aortic Aneurysm Susceptibility. Frontiers in physiology Wagenhäuser, M. U., Schellinger, I. N., Yoshino, T., Toyama, K., Kayama, Y., Deng, A., Guenther, S. P., Petzold, A., Mulorz, J., Mulorz, P., Hasenfuß, G., Ibing, W., Elvers, M., Schuster, A., Ramasubramanian, A. K., Adam, M., Schelzig, H., Spin, J. M., Raaz, U., Tsao, P. S. 2018; 9: 1459


    Aim: Arterial stiffness is a significant risk factor for many cardiovascular diseases, including abdominal aortic aneurysms (AAA). Nicotine, the major active ingredient of e-cigarettes and tobacco smoke, induces acute vasomotor effects that may temporarily increase arterial stiffness. Here, we investigated the effects of long-term nicotine exposure on structural aortic stiffness. Methods: Mice (C57BL/6) were infused with nicotine for 40 days (20 mg/kg/day). Arterial stiffness of the thoracic (TS) and abdominal (AS) aortic segments was analyzed using ultrasound (PWV, pulse wave velocity) and ex vivo pressure myograph measurements. For mechanistic studies, aortic matrix-metalloproteinase (MMP) expression and activity as well as medial elastin architecture were analyzed. Results: Global aortic stiffness increased with nicotine. In particular, local stiffening of the abdominal segment occurred after 10 days, while thoracic aortic stiffness was only increased after 40 days, resulting in aortic stiffness segmentation. Mechanistically, nicotine exposure enhanced expression of MMP-2/-9 and elastolytic activity in both aortic segments. Elastin degradation occurred in both segments; however, basal elastin levels were higher in the thoracic aorta. Finally, MMP-inhibition significantly reduced nicotine-induced MMP activity, elastin destruction, and aortic stiffening. Conclusion: Chronic nicotine exposure induces aortic MMP expression and structural aortic damage (elastin fragmentation), irreversibly increasing aortic stiffness. This process predominantly affects the abdominal aortic segment, presumably due in part to a lower basal elastin content. This novel phenomenon may help to explain the role of nicotine as a major risk factor for AAA formation and has health implications for ECIGs and other modes of nicotine delivery.

    View details for PubMedID 30429794

  • Retrograde aortomesenteric Bypass with left-retrorenal route - "French Bypass" in 16 cases of chronic mesenteric ischemia. Annals of vascular surgery Mulorz, J., Wagenhäuser, M. U., Janiszewski, Y. K., Dueppers, P., Simon, F., Schelzig, H., Duran, M. 2017


    There are several options for treating patients suffering from chronic mesenteric ischemia (CMI). One possibility contains bypass grafting following a left renal route to avoid inter alia kinking of the bypass. This study reviews the results of 16 patients suffering from CMI treated with this bypass technique, called "French Bypass" (FB).A retrospective study conducted between June 1, 2002, and December 31, 2015. Sixteen patients were included with an average age of 54.6 years (10 women) who were treated with FB. Risk factors, surgical course, and follow-up were evaluated.Average stay in hospital took 28.4 days, with mostly minor complications occurring. Overall, 4 cases of FB occlusion were diagnosed in between 30 days after surgery, of which 3 made interventions necessary. Primary patency rates were 75%/56%/56% after 12/24/60 months. Overall survival rate after 60 month was 78%.The FB is a sufficient option for treatment of CMI combining advantages of anterograde and retrograde bypass grafting, with comparable outcome to established techniques in visceral vessel reconstruction.

    View details for DOI 10.1016/j.avsg.2017.04.023

    View details for PubMedID 28483622

  • Oxidized (non)-regenerated cellulose affects fundamental cellular processes of wound healing SCIENTIFIC REPORTS Wagenhaeuser, M. U., Mulorz, J., Ibing, W., Simon, F., Spin, J. M., Schelzig, H., Oberhuber, A. 2016; 6


    In this study we investigated how hemostats such as oxidized regenerated cellulose (ORC, TABOTAMP) and oxidized non-regenerated cellulose (ONRC, RESORBA CELL) influence local cellular behavior and contraction of the extracellular matrix (ECM). Human stromal fibroblasts were inoculated in vitro with ORC and ONRC. Cell proliferation was assayed over time, and migration was evaluated by Live Cell imaging microscopy. Fibroblasts grown in collagen-gels were treated with ORC or ONRC, and ECM contraction was measured utilizing a contraction assay. An absolute pH decline was observed with both ORC and ONRC after 1 hour. Mean daily cell proliferation, migration and matrix contraction were more strongly inhibited by ONRC when compared with ORC (p < 0.05). When control media was pH-lowered to match the lower pH values typically seen with ORC and ONRC, significant differences in cell proliferation and migration were still observed between ONRC and ORC (p < 0.05). However, in these pH conditions, inhibition of matrix contraction was only significant for ONRC (p < 0.05). We find that ORC and ONRC inhibit fibroblast proliferation, migration and matrix contraction, and stronger inhibition of these essential cellular processes of wound healing were observed for ONRC when compared with ORC. These results will require further validation in future in vivo experiments to clarify the clinical implications for hemostat use in post-surgical wound healing.

    View details for DOI 10.1038/srep32238

    View details for Web of Science ID 000381867000001

    View details for PubMedID 27557881

    View details for PubMedCentralID PMC4997603